SummaryRates of domestic violence and the relative risk of premature death for women are higher in sub-Saharan Africa than in any other region. Yet we know remarkably little about the economic forces, incentives and constraints that drive discrimination against women in this region, making it hard to identify policy levers to address the problem. This project will help fill this gap.
I will investigate gender discrimination from two complementary perspectives. First, through the lens of economic history, I will investigate the forces driving trends in women’s relative well-being since slavery. To quantify the evolution of well-being of sub-Saharan women relative to men, I will use three types of historical data: anthropometric indicators (relative height), vital statistics (to compute numbers of missing women), and outcomes of formal and informal family law disputes. I will then investigate how major economic developments and changes in family laws differentially affected women’s welfare across ethnic groups with different norms on women’s roles and rights.
Second, using intra-household economic models, I will provide new insights into domestic violence and gender bias in access to crucial resources in present-day Africa. I will develop a new household model that incorporates gender identity and endogenous outside options to explore the relationship between women’s empowerment and the use of violence. Using the notion of strategic delegation, I will propose a new rationale for the separation of budgets often observed in African households and generate predictions of how improvements in women’s outside options affect welfare. Finally, with first hand data, I will investigate intra-household differences in nutrition and work effort in times of food shortage from the points of view of efficiency and equity. I will use activity trackers as an innovative means of collecting high quality data on work effort and thus overcome data limitations restricting the existing literature

Rates of domestic violence and the relative risk of premature death for women are higher in sub-Saharan Africa than in any other region. Yet we know remarkably little about the economic forces, incentives and constraints that drive discrimination against women in this region, making it hard to identify policy levers to address the problem. This project will help fill this gap.
I will investigate gender discrimination from two complementary perspectives. First, through the lens of economic history, I will investigate the forces driving trends in women’s relative well-being since slavery. To quantify the evolution of well-being of sub-Saharan women relative to men, I will use three types of historical data: anthropometric indicators (relative height), vital statistics (to compute numbers of missing women), and outcomes of formal and informal family law disputes. I will then investigate how major economic developments and changes in family laws differentially affected women’s welfare across ethnic groups with different norms on women’s roles and rights.
Second, using intra-household economic models, I will provide new insights into domestic violence and gender bias in access to crucial resources in present-day Africa. I will develop a new household model that incorporates gender identity and endogenous outside options to explore the relationship between women’s empowerment and the use of violence. Using the notion of strategic delegation, I will propose a new rationale for the separation of budgets often observed in African households and generate predictions of how improvements in women’s outside options affect welfare. Finally, with first hand data, I will investigate intra-household differences in nutrition and work effort in times of food shortage from the points of view of efficiency and equity. I will use activity trackers as an innovative means of collecting high quality data on work effort and thus overcome data limitations restricting the existing literature

Max ERC Funding

1 499 313 €

Duration

Start date: 2018-08-01, End date: 2023-07-31

Project acronymBacRafts

ProjectArchitecture of bacterial lipid rafts; inhibition of virulence and antibiotic resistance using raft-disassembling small molecules

SummaryMembranes of eukaryotic cells organize signal transduction proteins into microdomains or lipid rafts whose integrity is essential for numerous cellular processes. Lipid rafts has been considered a fundamental step to define the cellular complexity of eukaryotes, assuming that bacteria do not require such a sophisticated organization of their signaling networks. However, I have discovered that bacteria organize many signaling pathways in membrane microdomains similar to the eukaryotic lipid rafts. Perturbation of bacterial lipid rafts leads to a potent and simultaneous impairment of all raft-harbored signaling pathways. Consequently, the disassembly of lipid rafts in pathogens like Staphylococcus aureus generates a simultaneous inhibition of numerous infection-related processes that can be further explored to control bacterial infections. This unexpected sophistication in membrane organization is unprecedented in bacteria and hence, this proposal will explore the molecular basis of the assembly of bacterial lipid rafts and their role in the infection-related processes. These questions will be addressed in three main goals: First, I will elucidate the molecular components and the mechanism of assembly of bacterial lipid rafts using S. aureus as model organism. Second, I will dissect the molecular basis that links the functionality of the infection-related processes to the integrity of bacterial lipid rafts. Third, my collection of anti-raft small molecules that are able to disrupt lipid rafts will be tested as antimicrobial agents to prevent hospital-acquired infections, abrogate pre-existing infections and develop bacteria-free materials that can be used in clinical settings. I will use a number of molecular approaches in combination with cutting-edge techniques in flow cytometry, cell-imaging and transcriptomics to clarify the architecture and functionality of lipid rafts and demonstrate the feasibility of targeting lipid a new strategy for anti-microbial therapy.

Membranes of eukaryotic cells organize signal transduction proteins into microdomains or lipid rafts whose integrity is essential for numerous cellular processes. Lipid rafts has been considered a fundamental step to define the cellular complexity of eukaryotes, assuming that bacteria do not require such a sophisticated organization of their signaling networks. However, I have discovered that bacteria organize many signaling pathways in membrane microdomains similar to the eukaryotic lipid rafts. Perturbation of bacterial lipid rafts leads to a potent and simultaneous impairment of all raft-harbored signaling pathways. Consequently, the disassembly of lipid rafts in pathogens like Staphylococcus aureus generates a simultaneous inhibition of numerous infection-related processes that can be further explored to control bacterial infections. This unexpected sophistication in membrane organization is unprecedented in bacteria and hence, this proposal will explore the molecular basis of the assembly of bacterial lipid rafts and their role in the infection-related processes. These questions will be addressed in three main goals: First, I will elucidate the molecular components and the mechanism of assembly of bacterial lipid rafts using S. aureus as model organism. Second, I will dissect the molecular basis that links the functionality of the infection-related processes to the integrity of bacterial lipid rafts. Third, my collection of anti-raft small molecules that are able to disrupt lipid rafts will be tested as antimicrobial agents to prevent hospital-acquired infections, abrogate pre-existing infections and develop bacteria-free materials that can be used in clinical settings. I will use a number of molecular approaches in combination with cutting-edge techniques in flow cytometry, cell-imaging and transcriptomics to clarify the architecture and functionality of lipid rafts and demonstrate the feasibility of targeting lipid a new strategy for anti-microbial therapy.

SummaryThe actual view of cellular transformation and cancer progression supports the notion that cancer cells must undergo metabolic reprogramming in order to survive in a hostile environment. This field has experienced a renaissance in recent years, with the discovery of cancer genes regulating metabolic homeostasis, in turn being accepted as an emergent hallmark of cancer. Prostate cancer presents one of the highest incidences in men mostly in developed societies and exhibits a significant association with lifestyle environmental factors. Prostate cancer recurrence is thought to rely on a subpopulation of cancer cells with low-androgen requirements, high self-renewal potential and multidrug resistance, defined as cancer-initiating cells. However, whether this cancer cell fraction presents genuine metabolic properties that can be therapeutically relevant remains undefined. In CancerMetab, we aim to understand the potential benefit of monitoring and manipulating metabolism for prostate cancer prevention, detection and therapy. My group will carry out a multidisciplinary strategy, comprising cellular systems, genetic mouse models of prostate cancer, human epidemiological and clinical studies and bioinformatic analysis. The singularity of this proposal stems from the approach to the three key aspects that we propose to study. For prostate cancer prevention, we will use our faithful mouse model of prostate cancer to shed light on the contribution of obesity to prostate cancer. For prostate cancer detection, we will overcome the consistency issues of previously reported metabolic biomarkers by adding robustness to the human studies with mouse data integration. For prostate cancer therapy, we will focus on a cell population for which the metabolic requirements and the potential of targeting them for therapy have been overlooked to date, that is the prostate cancer-initiating cell compartment.

The actual view of cellular transformation and cancer progression supports the notion that cancer cells must undergo metabolic reprogramming in order to survive in a hostile environment. This field has experienced a renaissance in recent years, with the discovery of cancer genes regulating metabolic homeostasis, in turn being accepted as an emergent hallmark of cancer. Prostate cancer presents one of the highest incidences in men mostly in developed societies and exhibits a significant association with lifestyle environmental factors. Prostate cancer recurrence is thought to rely on a subpopulation of cancer cells with low-androgen requirements, high self-renewal potential and multidrug resistance, defined as cancer-initiating cells. However, whether this cancer cell fraction presents genuine metabolic properties that can be therapeutically relevant remains undefined. In CancerMetab, we aim to understand the potential benefit of monitoring and manipulating metabolism for prostate cancer prevention, detection and therapy. My group will carry out a multidisciplinary strategy, comprising cellular systems, genetic mouse models of prostate cancer, human epidemiological and clinical studies and bioinformatic analysis. The singularity of this proposal stems from the approach to the three key aspects that we propose to study. For prostate cancer prevention, we will use our faithful mouse model of prostate cancer to shed light on the contribution of obesity to prostate cancer. For prostate cancer detection, we will overcome the consistency issues of previously reported metabolic biomarkers by adding robustness to the human studies with mouse data integration. For prostate cancer therapy, we will focus on a cell population for which the metabolic requirements and the potential of targeting them for therapy have been overlooked to date, that is the prostate cancer-initiating cell compartment.

SummaryIn today’s globalized world, labor mobility is at the core of the political debate and a centerpiece for economic policy. The design of migration policies, such as selective, skill-biased, immigration policies, policies to encourage the integration of immigrants, or ones that facilitate geographical mobility to increase labor market opportunities of disadvantaged workers, requires a good understanding of a more fundamental issue: understanding the role of internal migration and immigration in shaping the career paths and human capital accumulation of workers. This project aims at providing a coherent analysis that allows us to understand the interactions between labor mobility and human capital accumulation, and their implications for economic policy design.
This project focuses on three main issues: labor mobility, labor market effects of immigration, and the interaction between the two. Our questions are: (a) What are the role of temporary and permanent contracts in shaping career paths and geographic mobility of workers? (b) Does the forgone human capital accumulation during a recession produce a lost generation? Is this alleviated by geographical mobility? (c) What is the role of geographical and occupational mobility in spreading or containing the effects of technological progress on wage inequality? (d) To what extent selective immigration policies maximize native workers’ prospects and wellbeing? (e) How can we increase degree of assimilation of immigrants?
To address these questions, we will develop dynamic equilibrium models that explicitly characterize human capital accumulation decisions of workers and how these decisions interact with migration. Our proposed models will introduce rich labor market structures and a variety of economic shocks. They will require the implementation of novel estimation methods, which we will also develop. The estimated models will be used to evaluate and design key economic policies for the labor market.

In today’s globalized world, labor mobility is at the core of the political debate and a centerpiece for economic policy. The design of migration policies, such as selective, skill-biased, immigration policies, policies to encourage the integration of immigrants, or ones that facilitate geographical mobility to increase labor market opportunities of disadvantaged workers, requires a good understanding of a more fundamental issue: understanding the role of internal migration and immigration in shaping the career paths and human capital accumulation of workers. This project aims at providing a coherent analysis that allows us to understand the interactions between labor mobility and human capital accumulation, and their implications for economic policy design.
This project focuses on three main issues: labor mobility, labor market effects of immigration, and the interaction between the two. Our questions are: (a) What are the role of temporary and permanent contracts in shaping career paths and geographic mobility of workers? (b) Does the forgone human capital accumulation during a recession produce a lost generation? Is this alleviated by geographical mobility? (c) What is the role of geographical and occupational mobility in spreading or containing the effects of technological progress on wage inequality? (d) To what extent selective immigration policies maximize native workers’ prospects and wellbeing? (e) How can we increase degree of assimilation of immigrants?
To address these questions, we will develop dynamic equilibrium models that explicitly characterize human capital accumulation decisions of workers and how these decisions interact with migration. Our proposed models will introduce rich labor market structures and a variety of economic shocks. They will require the implementation of novel estimation methods, which we will also develop. The estimated models will be used to evaluate and design key economic policies for the labor market.

Max ERC Funding

1 400 250 €

Duration

Start date: 2018-11-01, End date: 2023-10-31

Project acronymELONGAN

ProjectGene editing and in vitro approaches to understand conceptus elongation in ungulates

SummaryIn contrast to human or rodent embryos, ungulate embryos do not implant into the uterus right after blastocyst hatching. Before implantation, the hatched ungulate blastocyst must undergo dramatic morphological changes characterized by cell differentiation, proliferation and migration processes leading to the development of extra-embryonic membranes, the appearance of a flat embryonic disc and gastrulation. This prolonged preimplantation development is termed conceptus elongation and deficiencies on this process constitute the most frequent cause of reproductive failures in ungulates, including the 4 most relevant mammalian livestock species in Europe. The purpose of this project is to elucidate the factors involved in conceptus elongation by gene editing and in vitro culture approaches. A first objective will be to identify key genes involved in differentiation processes by RNA-seq analysis of different embryo derivatives from bovine conceptuses at different developmental stages. Subsequently, the function of some of the genes identified as well as others known to play a crucial role in mouse development or putatively involved in embryo-maternal interactions will be assessed. For this aim, bovine embryos in which a candidate gene has been ablated (KO) will be generated by CRISPR and transferred to recipient females to assess in vivo the function of such particular gene on conceptus development. A second set of experiments pursue the development of an in vitro system for conceptus elongation that would bypass the requirement for in vivo experiments. For this aim we will perform metabolomics and proteomics analyses of bovine uterine fluid at different stages and will use these data to rationally develop a culture system able to sustain conceptus development. The knowledge generated by this project will serve to develop strategies to enhance farming profitability by reducing embryonic loss and to understand Developmental Biology questions unanswered by the mouse model.

In contrast to human or rodent embryos, ungulate embryos do not implant into the uterus right after blastocyst hatching. Before implantation, the hatched ungulate blastocyst must undergo dramatic morphological changes characterized by cell differentiation, proliferation and migration processes leading to the development of extra-embryonic membranes, the appearance of a flat embryonic disc and gastrulation. This prolonged preimplantation development is termed conceptus elongation and deficiencies on this process constitute the most frequent cause of reproductive failures in ungulates, including the 4 most relevant mammalian livestock species in Europe. The purpose of this project is to elucidate the factors involved in conceptus elongation by gene editing and in vitro culture approaches. A first objective will be to identify key genes involved in differentiation processes by RNA-seq analysis of different embryo derivatives from bovine conceptuses at different developmental stages. Subsequently, the function of some of the genes identified as well as others known to play a crucial role in mouse development or putatively involved in embryo-maternal interactions will be assessed. For this aim, bovine embryos in which a candidate gene has been ablated (KO) will be generated by CRISPR and transferred to recipient females to assess in vivo the function of such particular gene on conceptus development. A second set of experiments pursue the development of an in vitro system for conceptus elongation that would bypass the requirement for in vivo experiments. For this aim we will perform metabolomics and proteomics analyses of bovine uterine fluid at different stages and will use these data to rationally develop a culture system able to sustain conceptus development. The knowledge generated by this project will serve to develop strategies to enhance farming profitability by reducing embryonic loss and to understand Developmental Biology questions unanswered by the mouse model.

Max ERC Funding

1 480 880 €

Duration

Start date: 2017-10-01, End date: 2022-09-30

Project acronymENIGMO

Project"Gut microbiota, innate immunity and endocannabinoid system interactions link metabolic inflammation with the hallmarks of obesity and type 2 diabetes"

Researcher (PI)Patrice Daniel Cani

Host Institution (HI)UNIVERSITE CATHOLIQUE DE LOUVAIN

Call DetailsStarting Grant (StG), LS4, ERC-2013-StG

Summary"Obesity and type 2 diabetes are characterized by metabolic inflammation and an altered endocannabinoid system (eCB) tone. We have provided evidence that gut microbiota modulate both intestinal and adipose tissue eCB system tone. Insulin resistance and inflammation have been linked to microbiota-host interaction via different Toll-Like Receptors (TLR’s). Our preliminary data show that tamoxifen-induced epithelial intestinal cells deletion of the key signalling adaptor MyD88 (myeloid differentiation primary-response gene 88), that encompass most of the TLR’s, protect mice against diet-induced obesity and inflammation. A phenomenon closely linked with changes in the intestinal eCB system tone and antimicrobial peptides production. Moreover, we discovered that the recently identified bacteria living in the mucus layer, namely Akkermansia muciniphila, plays a central role in the regulation of host energy metabolism by putative mechanisms linking both the intestinal eCB system and the innate immune system. Thus these preliminary data support the existence of unidentified mechanisms linking the innate immune system, the gut microbiota and host metabolism. In this high-risk/high-gain research program, we propose to elucidate what could be one of the most fundamental processes shared by different key hallmarks of obesity and related diseases. A careful and thorough analysis of the molecular and cellular events linking gut microbiota, the innate immune system and eCB system in specific organs has the potential to unravel new therapeutic targets. We anticipate the key role of MyD88 and the enzyme NAPE-PLD (N-acylphosphatidylethanolamine phospholipase-D) involved in the synthesis of N-acylethanolamines family to be key determinant in such pathophysiological aspects. Thus, these approaches could provide different perspectives about disease pathogenesis and knowledge-based evidence of new therapeutic options for obesity and associated metabolic disorders in the future."

"Obesity and type 2 diabetes are characterized by metabolic inflammation and an altered endocannabinoid system (eCB) tone. We have provided evidence that gut microbiota modulate both intestinal and adipose tissue eCB system tone. Insulin resistance and inflammation have been linked to microbiota-host interaction via different Toll-Like Receptors (TLR’s). Our preliminary data show that tamoxifen-induced epithelial intestinal cells deletion of the key signalling adaptor MyD88 (myeloid differentiation primary-response gene 88), that encompass most of the TLR’s, protect mice against diet-induced obesity and inflammation. A phenomenon closely linked with changes in the intestinal eCB system tone and antimicrobial peptides production. Moreover, we discovered that the recently identified bacteria living in the mucus layer, namely Akkermansia muciniphila, plays a central role in the regulation of host energy metabolism by putative mechanisms linking both the intestinal eCB system and the innate immune system. Thus these preliminary data support the existence of unidentified mechanisms linking the innate immune system, the gut microbiota and host metabolism. In this high-risk/high-gain research program, we propose to elucidate what could be one of the most fundamental processes shared by different key hallmarks of obesity and related diseases. A careful and thorough analysis of the molecular and cellular events linking gut microbiota, the innate immune system and eCB system in specific organs has the potential to unravel new therapeutic targets. We anticipate the key role of MyD88 and the enzyme NAPE-PLD (N-acylphosphatidylethanolamine phospholipase-D) involved in the synthesis of N-acylethanolamines family to be key determinant in such pathophysiological aspects. Thus, these approaches could provide different perspectives about disease pathogenesis and knowledge-based evidence of new therapeutic options for obesity and associated metabolic disorders in the future."

Max ERC Funding

1 494 640 €

Duration

Start date: 2013-10-01, End date: 2018-09-30

Project acronymEXTREME

ProjectThe Rise and Fall of Populism and Extremism

Researcher (PI)Maria PETROVA

Host Institution (HI)UNIVERSIDAD POMPEU FABRA

Call DetailsStarting Grant (StG), SH1, ERC-2018-STG

SummaryIn the recent years in advanced democracies there has been a wave of electoral successes of populist politicians supporting extreme messages. Is populism caused by negative economic shocks? If so, what are the mechanisms? What explains heterogeneity in responses to such shocks? In this project, I will test empirically if personal experiences, information environment, and their interaction with aggregate economic shocks shape people’s political decisions. The project consists of three parts.
First, I will study how personal employment histories, potentially affected by globalization and technological shocks, individual predispositions, and information environment influenced voting for Trump. I will use a unique database of more than 40 million resumes for the period 2010-2016, the largest available repository of resumes of job-seekers in the US, which was not previously used in academic research, and match it with zipcode-level economic and voting variables.
Second, I will study how negative social experiences during the formative years affect subsequent labor market outcomes, antisocial behavior, and the support of populist agenda. I will examine how corporal punishment in schools in UK affected subsequent educational attainment, employment, antisocial behavior, and voting for UKIP and Brexit. I will digitize archival records on regulations and practice of corporal punishment in different educational authorities in the UK during 1970-80s, combining it with contemporary outcomes.
Third, I will examine what makes people actively resist extremist regimes even when it is associated with high personal costs. I will study a historical example of resistance to Nazi regime in Germany during the WWII, which provides unique methodological opportunity to study determinants of resistance to extremism in a high stake environment. I will use a self-collected dataset on treason cases to measure resistance, combining it with data on bombing and exposure to foreign propaganda.

In the recent years in advanced democracies there has been a wave of electoral successes of populist politicians supporting extreme messages. Is populism caused by negative economic shocks? If so, what are the mechanisms? What explains heterogeneity in responses to such shocks? In this project, I will test empirically if personal experiences, information environment, and their interaction with aggregate economic shocks shape people’s political decisions. The project consists of three parts.
First, I will study how personal employment histories, potentially affected by globalization and technological shocks, individual predispositions, and information environment influenced voting for Trump. I will use a unique database of more than 40 million resumes for the period 2010-2016, the largest available repository of resumes of job-seekers in the US, which was not previously used in academic research, and match it with zipcode-level economic and voting variables.
Second, I will study how negative social experiences during the formative years affect subsequent labor market outcomes, antisocial behavior, and the support of populist agenda. I will examine how corporal punishment in schools in UK affected subsequent educational attainment, employment, antisocial behavior, and voting for UKIP and Brexit. I will digitize archival records on regulations and practice of corporal punishment in different educational authorities in the UK during 1970-80s, combining it with contemporary outcomes.
Third, I will examine what makes people actively resist extremist regimes even when it is associated with high personal costs. I will study a historical example of resistance to Nazi regime in Germany during the WWII, which provides unique methodological opportunity to study determinants of resistance to extremism in a high stake environment. I will use a self-collected dataset on treason cases to measure resistance, combining it with data on bombing and exposure to foreign propaganda.

SummaryRecent global warming is acting across ecosystems and threatening biodiversity. Yet, due to slow responses, many biological communities are lagging behind warming of the macroclimate (the climate of a large geographic region). The buffering of microclimates near the ground measured in localized areas, arising from terrain features such as vegetation and topography, can explain why many species are lagging behind macroclimate warming. However, almost all studies ignore the effects of microclimatic buffering and key uncertainties still exist about this mechanism. Microclimates are particularly evident in forests, where understorey habitats are buffered by overstorey trees. In temperate forests, the understorey contains the vast majority of plant diversity and plays an essential role in driving ecosystem processes.
The overall goal of FORMICA (FORest MICroclimate Assessment) is to quantify and understand the role of microclimatic buffering in modulating forest understorey plant responses to macroclimate warming. We will perform the best assessment to date of the effects of microclimates on plants by applying microtemperature loggers, experimental heating, fluorescent tubes and a large-scale transplant experiment in temperate forests across Europe. For the first time, plant data from the individual to ecosystem level will be related to microclimate along wide temperature gradients and forest management regimes. The empirical results will then be integrated in cutting-edge demographic distribution models to forecast plant diversity in temperate forests as macroclimate warms.
FORMICA will provide the first integrative study on microclimatic buffering of macroclimate warming in forests. Interdisciplinary concepts and methods will be applied, including from climatology, forestry and ecology. FORMICA will reshape our current understanding of the impacts of climate change on forests and help land managers and policy makers to develop urgently needed adaptation strategies.

Recent global warming is acting across ecosystems and threatening biodiversity. Yet, due to slow responses, many biological communities are lagging behind warming of the macroclimate (the climate of a large geographic region). The buffering of microclimates near the ground measured in localized areas, arising from terrain features such as vegetation and topography, can explain why many species are lagging behind macroclimate warming. However, almost all studies ignore the effects of microclimatic buffering and key uncertainties still exist about this mechanism. Microclimates are particularly evident in forests, where understorey habitats are buffered by overstorey trees. In temperate forests, the understorey contains the vast majority of plant diversity and plays an essential role in driving ecosystem processes.
The overall goal of FORMICA (FORest MICroclimate Assessment) is to quantify and understand the role of microclimatic buffering in modulating forest understorey plant responses to macroclimate warming. We will perform the best assessment to date of the effects of microclimates on plants by applying microtemperature loggers, experimental heating, fluorescent tubes and a large-scale transplant experiment in temperate forests across Europe. For the first time, plant data from the individual to ecosystem level will be related to microclimate along wide temperature gradients and forest management regimes. The empirical results will then be integrated in cutting-edge demographic distribution models to forecast plant diversity in temperate forests as macroclimate warms.
FORMICA will provide the first integrative study on microclimatic buffering of macroclimate warming in forests. Interdisciplinary concepts and methods will be applied, including from climatology, forestry and ecology. FORMICA will reshape our current understanding of the impacts of climate change on forests and help land managers and policy makers to develop urgently needed adaptation strategies.

SummaryThe mechanisms underlying lung homeostasis are of fundamental biological importance and have critical implications for the prevention of immune-mediated diseases such as asthma. We have demonstrated that lung Interstitial Macrophages (IM) exhibit a tolerogenic profile and are able to prevent and limit the development of aberrant immune responses against allergens, thus underscoring their role as crucial regulators of lung homeostasis. In addition, we have shown that IM could expand from monocyte precursors upon host exposure to bacterial unmethylated CpG-DNA, resulting in robust protection against allergic asthma. To date, however, IM have only been characterized as a bulk population in functional studies, and little is known about the tissue-instructive signals, specific transcription factors and differentiation programs which contribute to determining their identity (ID) and function, as proposed by the macrophage niche model. We have developed an innovative transgenic tool to selectively target IM which, in combination with high dimensional single cell technologies, will allow us to (1) define the precise ID of IM, i.e. their spatial organization, heterogeneity, molecular signature and the specific TF governing their differentiation and function; (2) investigate how IM ID is imprinted by the local niche to sustain lung homeostasis. Specifically, we aim to identify the epithelial cell-derived chemo-attractive signals controlling IM precursor recruitment and to elucidate the contribution of the lung cholinergic nervous system to IM ID and lung homeostasis. This research will increase our understanding of the basic mechanisms underlying the fine-tuning of tolerogenic IM and will thus provide robust foundations for novel IM-targeted approaches promoting health and preventing airway diseases in which IM (dys)functions have been implicated.

The mechanisms underlying lung homeostasis are of fundamental biological importance and have critical implications for the prevention of immune-mediated diseases such as asthma. We have demonstrated that lung Interstitial Macrophages (IM) exhibit a tolerogenic profile and are able to prevent and limit the development of aberrant immune responses against allergens, thus underscoring their role as crucial regulators of lung homeostasis. In addition, we have shown that IM could expand from monocyte precursors upon host exposure to bacterial unmethylated CpG-DNA, resulting in robust protection against allergic asthma. To date, however, IM have only been characterized as a bulk population in functional studies, and little is known about the tissue-instructive signals, specific transcription factors and differentiation programs which contribute to determining their identity (ID) and function, as proposed by the macrophage niche model. We have developed an innovative transgenic tool to selectively target IM which, in combination with high dimensional single cell technologies, will allow us to (1) define the precise ID of IM, i.e. their spatial organization, heterogeneity, molecular signature and the specific TF governing their differentiation and function; (2) investigate how IM ID is imprinted by the local niche to sustain lung homeostasis. Specifically, we aim to identify the epithelial cell-derived chemo-attractive signals controlling IM precursor recruitment and to elucidate the contribution of the lung cholinergic nervous system to IM ID and lung homeostasis. This research will increase our understanding of the basic mechanisms underlying the fine-tuning of tolerogenic IM and will thus provide robust foundations for novel IM-targeted approaches promoting health and preventing airway diseases in which IM (dys)functions have been implicated.

SummaryPlant nutrition is essential to understand any physiological process in plant biology, as well as to improve crops, and agricultural practices. The root microbiome plays an important role in plant nutrition. The best characterized microbiome elements are two plant endosymbionts: arbuscular mycorrhizal fungi (AMF) and rhizobia. AMF are responsible for delivering most of the mineral nutrients required by the host plant. Similarly, rhizobia in legume nodules provide the vast majority of the nitrogen requirements. Given their importance for plant nutrition a significant effort in understanding macronutrient exchange among the symbionts has been made. However, very little is known about metal micronutrient exchange.
This is in contrast to the role of metals as essential nutrients for life (30-50 % of the proteins are metalloproteins) and to the yield-limiting effect that low soil metal bioavailability has worldwide. AMF are a source of metals, transferring the incorporated metals to the host,. Nitrogen-fixing rhizobia in mature nodules act as metal sinks, since the main enzymes required are highly expressed metalloproteins. We hypothesize that by changing the expression levels of the metal transporters involved, we will increase nitrogen fixation rates and increase plant metal uptake, resulting in higher crop production and fruit metal biofortification. Towards this goal, we will answer: i) How are metals incorporated from the AMF into the plant?, ii) How are metals delivered to the nodule?, iii) How are metals recovered from senescent nodules?, and iv) How does the natural variation of symbiotic-specific metal transporters affect yields and metal content of the fruit? In this project, we will use a multidisciplinary approach that involves metallotranscriptomics, plant physiology and molecular biology, and state-of-the art synchrotron based X-ray fluorescence to study metal distributions.

Plant nutrition is essential to understand any physiological process in plant biology, as well as to improve crops, and agricultural practices. The root microbiome plays an important role in plant nutrition. The best characterized microbiome elements are two plant endosymbionts: arbuscular mycorrhizal fungi (AMF) and rhizobia. AMF are responsible for delivering most of the mineral nutrients required by the host plant. Similarly, rhizobia in legume nodules provide the vast majority of the nitrogen requirements. Given their importance for plant nutrition a significant effort in understanding macronutrient exchange among the symbionts has been made. However, very little is known about metal micronutrient exchange.
This is in contrast to the role of metals as essential nutrients for life (30-50 % of the proteins are metalloproteins) and to the yield-limiting effect that low soil metal bioavailability has worldwide. AMF are a source of metals, transferring the incorporated metals to the host,. Nitrogen-fixing rhizobia in mature nodules act as metal sinks, since the main enzymes required are highly expressed metalloproteins. We hypothesize that by changing the expression levels of the metal transporters involved, we will increase nitrogen fixation rates and increase plant metal uptake, resulting in higher crop production and fruit metal biofortification. Towards this goal, we will answer: i) How are metals incorporated from the AMF into the plant?, ii) How are metals delivered to the nodule?, iii) How are metals recovered from senescent nodules?, and iv) How does the natural variation of symbiotic-specific metal transporters affect yields and metal content of the fruit? In this project, we will use a multidisciplinary approach that involves metallotranscriptomics, plant physiology and molecular biology, and state-of-the art synchrotron based X-ray fluorescence to study metal distributions.

Max ERC Funding

1 499 405 €

Duration

Start date: 2014-02-01, End date: 2019-01-31

Project acronymMIRAGE

ProjectIndependence and quality of mass Media in the InteRnet AGE

Researcher (PI)Ruben Durante

Host Institution (HI)UNIVERSIDAD POMPEU FABRA

Call DetailsStarting Grant (StG), SH1, ERC-2017-STG

SummaryThe Internet was expected to make citizens considerably more informed and better able to hold politicians and powerful interests accountable. Many predicted it would also effectively complement traditional media and improve news reporting. These expectations have not been met. There is no evidence that citizens have become more informed; they have, however, become more ideologically polarized, possibly due to online media overexposing users to like-minded content. At the same time, traditional media are struggling: competition from online platforms has slashed advertising revenues forcing newspapers to close or downsize. These changes risk undermining the quality of reporting and making media more vulnerable to capture by special interests.
My project examines how the Internet has transformed the way news is produced and disseminated, both directly and through its influence on traditional media, and its ultimate effect on media independence and content quality. To this end, I tackle four distinct but intertwined questions. First, I examine to what extent Google search results are tailored to users’ political views, and whether personalized results increase ideological polarization. Second, I study how lower advertising revenues affect newspapers’ organization and content quality by exploiting the staggered introduction of advertising platform Craigslist across the US. Third, I examine how media dependence on advertisers influences news bias by testing the relationship between advertising spending by car manufacturers and coverage of car safety recalls in US newspapers. Finally, I study how the dependence of media on banks affects coverage of financial issues; focusing on Europe’s sovereign debt crisis, I test whether newspapers linked to banks with higher exposure to risky debt endorsed different crisis-management measures.
My results will shed light on the deep transformations the media industry is undergoing and their implications for the quality of democracy.

The Internet was expected to make citizens considerably more informed and better able to hold politicians and powerful interests accountable. Many predicted it would also effectively complement traditional media and improve news reporting. These expectations have not been met. There is no evidence that citizens have become more informed; they have, however, become more ideologically polarized, possibly due to online media overexposing users to like-minded content. At the same time, traditional media are struggling: competition from online platforms has slashed advertising revenues forcing newspapers to close or downsize. These changes risk undermining the quality of reporting and making media more vulnerable to capture by special interests.
My project examines how the Internet has transformed the way news is produced and disseminated, both directly and through its influence on traditional media, and its ultimate effect on media independence and content quality. To this end, I tackle four distinct but intertwined questions. First, I examine to what extent Google search results are tailored to users’ political views, and whether personalized results increase ideological polarization. Second, I study how lower advertising revenues affect newspapers’ organization and content quality by exploiting the staggered introduction of advertising platform Craigslist across the US. Third, I examine how media dependence on advertisers influences news bias by testing the relationship between advertising spending by car manufacturers and coverage of car safety recalls in US newspapers. Finally, I study how the dependence of media on banks affects coverage of financial issues; focusing on Europe’s sovereign debt crisis, I test whether newspapers linked to banks with higher exposure to risky debt endorsed different crisis-management measures.
My results will shed light on the deep transformations the media industry is undergoing and their implications for the quality of democracy.

SummaryEvery year, the world economy invests a large amount of resources to improve or develop transport infrastructure. How should these investments be allocated to maximize social welfare? In this proposal, I propose to develop and apply new methods to study optimal transport networks in general-equilibrium models of international trade, urban economics and economic geography. The methodology will build on recent work (Fajgelbaum and Schaal, 2017), in which my coauthor and I studied the network design problem in a general neoclassical trade framework.
In the first project, I develop a new framework to analyze optimal infrastructure investment in an urban setting. The model features people commuting between residential areas and business districts as well as a choice over the mode of transportation. We plan to evaluate the framework to historical data about specific cities.
In the second project, I propose and implement an new algorithm to compute optimal transport networks in the presence of increasing returns to transport, a likely prominent feature of real-world networks. The algorithm applies a branch-and-bound method in a series of geometric programming relaxations of the problem.
In the third project, I study the dynamic evolution of actual transport networks using satellite data from the US, India and Mexico. In the spirit of Hsieh and Klenow (2007), I use the model to measure distortions in the placement of roads between rich and poor countries.
In the fourth project, I study the inefficiencies and welfare losses associated with political economy frictions among governments and planning agencies. I use the model to identify inefficiencies and relate them to measures of institutions and political outcomes.
In the final project, I propose a new explanation behind the Zipf’s law distribution of city sizes. I show that Zipf’s law may result from particular topological properties of optimal transport networks that allocate resources efficiently in space.

Every year, the world economy invests a large amount of resources to improve or develop transport infrastructure. How should these investments be allocated to maximize social welfare? In this proposal, I propose to develop and apply new methods to study optimal transport networks in general-equilibrium models of international trade, urban economics and economic geography. The methodology will build on recent work (Fajgelbaum and Schaal, 2017), in which my coauthor and I studied the network design problem in a general neoclassical trade framework.
In the first project, I develop a new framework to analyze optimal infrastructure investment in an urban setting. The model features people commuting between residential areas and business districts as well as a choice over the mode of transportation. We plan to evaluate the framework to historical data about specific cities.
In the second project, I propose and implement an new algorithm to compute optimal transport networks in the presence of increasing returns to transport, a likely prominent feature of real-world networks. The algorithm applies a branch-and-bound method in a series of geometric programming relaxations of the problem.
In the third project, I study the dynamic evolution of actual transport networks using satellite data from the US, India and Mexico. In the spirit of Hsieh and Klenow (2007), I use the model to measure distortions in the placement of roads between rich and poor countries.
In the fourth project, I study the inefficiencies and welfare losses associated with political economy frictions among governments and planning agencies. I use the model to identify inefficiencies and relate them to measures of institutions and political outcomes.
In the final project, I propose a new explanation behind the Zipf’s law distribution of city sizes. I show that Zipf’s law may result from particular topological properties of optimal transport networks that allocate resources efficiently in space.

Max ERC Funding

887 500 €

Duration

Start date: 2019-01-01, End date: 2023-12-31

Project acronymPLASREVOLUTION

ProjectUnderstanding the evolution of plasmid-mediated antibiotic resistance in real life scenarios

Researcher (PI)Alvaro SAN MILLAN

Host Institution (HI)SERVICIO MADRILENO DE SALUD

Call DetailsStarting Grant (StG), LS8, ERC-2017-STG

SummaryAntibiotics are essential tools in modern medicine and are indispensable not only for the treatment of infectious diseases but also to support other key interventions such as surgery and cancer chemotherapy. However, the extensive and inappropriate use of antibiotics has fuelled the spread of resistance mechanisms in pathogenic bacteria, leading to the dawn of a post-antibiotic era. Plasmids play a pivotal role in the evolution of antibiotic resistance (AR) because they drive the horizontal transfer of resistance genes between pathogenic bacteria by conjugation. Some of these plasmid-bacterium associations become particularly successful, creating superbugs that spread uncontrollably in clinical settings. The rise of these clones is mainly constricted because plasmids entail a fitness cost when they arrive in a new bacterial host. This cost can be subsequently alleviated through compensatory adaptation during plasmid-bacterium coevolution. Despite the importance of this cost-compensation dynamic in the evolution of plasmid-mediated AR, it remains completely unexplored in clinical contexts. In this project I plan to bridge this gap by exploring the genetic basis underlying the evolution of plasmid-mediated AR in clinically relevant scenarios. We will study, for the first time, the intra-patient transmission, fitness cost and adaptation of AR plasmids in the gut microbiome of hospitalized patients (obj. 1). We will analyse the molecular mechanisms that determine the success of AR plasmids and bacterial clone associations (obj. 2). Finally, we will develop new technology to test how antibiotic treatments affect AR plasmids dynamics in the gut microbiome at an unprecedentedly high-resolution (obj. 3). This ground-breaking project will allow a new understanding of the evolution of plasmid-mediated AR in real life, opening new research avenues and providing a major step towards meeting one of the central challenges facing our society: controlling the spread of AR.

Antibiotics are essential tools in modern medicine and are indispensable not only for the treatment of infectious diseases but also to support other key interventions such as surgery and cancer chemotherapy. However, the extensive and inappropriate use of antibiotics has fuelled the spread of resistance mechanisms in pathogenic bacteria, leading to the dawn of a post-antibiotic era. Plasmids play a pivotal role in the evolution of antibiotic resistance (AR) because they drive the horizontal transfer of resistance genes between pathogenic bacteria by conjugation. Some of these plasmid-bacterium associations become particularly successful, creating superbugs that spread uncontrollably in clinical settings. The rise of these clones is mainly constricted because plasmids entail a fitness cost when they arrive in a new bacterial host. This cost can be subsequently alleviated through compensatory adaptation during plasmid-bacterium coevolution. Despite the importance of this cost-compensation dynamic in the evolution of plasmid-mediated AR, it remains completely unexplored in clinical contexts. In this project I plan to bridge this gap by exploring the genetic basis underlying the evolution of plasmid-mediated AR in clinically relevant scenarios. We will study, for the first time, the intra-patient transmission, fitness cost and adaptation of AR plasmids in the gut microbiome of hospitalized patients (obj. 1). We will analyse the molecular mechanisms that determine the success of AR plasmids and bacterial clone associations (obj. 2). Finally, we will develop new technology to test how antibiotic treatments affect AR plasmids dynamics in the gut microbiome at an unprecedentedly high-resolution (obj. 3). This ground-breaking project will allow a new understanding of the evolution of plasmid-mediated AR in real life, opening new research avenues and providing a major step towards meeting one of the central challenges facing our society: controlling the spread of AR.

Max ERC Funding

1 497 314 €

Duration

Start date: 2018-02-01, End date: 2023-01-31

Project acronymRIBOCANCER

ProjectRibosome defects in cancer

Researcher (PI)Kim Diana Lea De Keersmaecker

Host Institution (HI)KATHOLIEKE UNIVERSITEIT LEUVEN

Call DetailsStarting Grant (StG), LS4, ERC-2013-StG

Summary"Cancer cells are defective in vital cell functions such as cell cycle control and response to growth signals. We found that cancer cells acquire defects in yet another vital function: translation of mRNA into proteins. We saw that 9.8% of children with T-cell leukemia (T-ALL) harbor acquired mutations in the ribosome, the cellular protein translation factory. We found mutations in RPL10, RPL5 and RPL22, 3 proteins of the large 60S ribosomal subunit. Strikingly, 6.5% of T-ALL patients had the same RPL10 R98S missense mutation. Although congenital ribosome defects were previously linked to higher cancer risk, the concept that defects in the ribosome are acquired during life and are selected for in cancer is novel. In addition, it is currently not understood by what mechanism ribosome defects are carcinogenic.
Patients with inherited ribosome defects are predisposed to all types of cancer. Therefore, other cancers than T-ALL may show acquired defects in the ribosome and I want to explore the prevalence of acquired ribosome defects in various cancer types. Second, I want to explore by which mechanism ribosome mutations promote cancer. Initially, I will focus on the RPL10 R98S mutation, the most frequent acquired ribosome defect we found so far. We will test the effect of RPL10 R98S on cell behavior parameters such as self-renewal capacity and resistance to apoptosis. I hypothesize that altered translation of a subset of cellular mRNAs, including mRNAs coding major tumor suppressors or oncogenes, may explain the oncogenic action of RPL10 R98S. Therefore, we will identify all mRNAs with altered translation efficiency or fidelity in RPL10 R98S cells. In addition, we will test if RPL10 R98S promotes cancer by altering extra-ribosomal roles of RPL10 or by driving inactivation of the TP53 pathway. Finally, acquired ribosome defects may represent a novel target for cancer therapy and we will test if ribosome defective cancer cells are hypersensitive to translation inhibitors."

"Cancer cells are defective in vital cell functions such as cell cycle control and response to growth signals. We found that cancer cells acquire defects in yet another vital function: translation of mRNA into proteins. We saw that 9.8% of children with T-cell leukemia (T-ALL) harbor acquired mutations in the ribosome, the cellular protein translation factory. We found mutations in RPL10, RPL5 and RPL22, 3 proteins of the large 60S ribosomal subunit. Strikingly, 6.5% of T-ALL patients had the same RPL10 R98S missense mutation. Although congenital ribosome defects were previously linked to higher cancer risk, the concept that defects in the ribosome are acquired during life and are selected for in cancer is novel. In addition, it is currently not understood by what mechanism ribosome defects are carcinogenic.
Patients with inherited ribosome defects are predisposed to all types of cancer. Therefore, other cancers than T-ALL may show acquired defects in the ribosome and I want to explore the prevalence of acquired ribosome defects in various cancer types. Second, I want to explore by which mechanism ribosome mutations promote cancer. Initially, I will focus on the RPL10 R98S mutation, the most frequent acquired ribosome defect we found so far. We will test the effect of RPL10 R98S on cell behavior parameters such as self-renewal capacity and resistance to apoptosis. I hypothesize that altered translation of a subset of cellular mRNAs, including mRNAs coding major tumor suppressors or oncogenes, may explain the oncogenic action of RPL10 R98S. Therefore, we will identify all mRNAs with altered translation efficiency or fidelity in RPL10 R98S cells. In addition, we will test if RPL10 R98S promotes cancer by altering extra-ribosomal roles of RPL10 or by driving inactivation of the TP53 pathway. Finally, acquired ribosome defects may represent a novel target for cancer therapy and we will test if ribosome defective cancer cells are hypersensitive to translation inhibitors."

SummaryGlobal food security will remain a worldwide concern for the next 50 years and beyond. Agricultural production undergoes an increasing pressure by global anthropogenic changes, including rising population, increased protein demands and climatic extremes. Because of the immediate and dynamic nature of these changes, productivity monitoring measures are urgently needed to ensure both the stability and continued increase of the global food supply. Europe has expressed ambitions to keep its fingers on the pulse of its agricultural lands. In response to that, this proposal - named SENTIFLEX - is dedicated to developing a European vegetation productivity monitoring facility based on the synergy of Sentinel-3 (S3) with FLEX satellite fluorescence data. ESA's 8th Earth Explorer FLEX is the first mission specifically designed to globally measure Sun-Induced chlorophyll Fluorescence (SIF) emission from terrestrial vegetation. These two European Earth observation missions offer immense possibilities to increase our knowledge of the basic functioning of the Earth’s vegetation, i.e., the photosynthetic activity of plants resulting in carbon fixation. Two complementary approaches are envisioned to realize quantification of photosynthesis through satellite SIF and S3. First, the work seeks to advance the science in establishing and consolidating relationships between canopy-leaving SIF and unbiased estimates of photosynthesis of the plants, thereby disentangling the role of dynamic vegetative and atmospheric variables. Second, consolidated relationships between SIF and photosynthesis will be used to build a FLEX-S3 data processing assimilation scheme through process-based vegetation models that will deliver spatiotemporally highly resolved information on Europe’s vegetation productivity. To streamline all these datasets into a prototype vegetation productivity monitoring facility, new data processing concepts will be introduced such as the emulation of radiative transfer models.

Global food security will remain a worldwide concern for the next 50 years and beyond. Agricultural production undergoes an increasing pressure by global anthropogenic changes, including rising population, increased protein demands and climatic extremes. Because of the immediate and dynamic nature of these changes, productivity monitoring measures are urgently needed to ensure both the stability and continued increase of the global food supply. Europe has expressed ambitions to keep its fingers on the pulse of its agricultural lands. In response to that, this proposal - named SENTIFLEX - is dedicated to developing a European vegetation productivity monitoring facility based on the synergy of Sentinel-3 (S3) with FLEX satellite fluorescence data. ESA's 8th Earth Explorer FLEX is the first mission specifically designed to globally measure Sun-Induced chlorophyll Fluorescence (SIF) emission from terrestrial vegetation. These two European Earth observation missions offer immense possibilities to increase our knowledge of the basic functioning of the Earth’s vegetation, i.e., the photosynthetic activity of plants resulting in carbon fixation. Two complementary approaches are envisioned to realize quantification of photosynthesis through satellite SIF and S3. First, the work seeks to advance the science in establishing and consolidating relationships between canopy-leaving SIF and unbiased estimates of photosynthesis of the plants, thereby disentangling the role of dynamic vegetative and atmospheric variables. Second, consolidated relationships between SIF and photosynthesis will be used to build a FLEX-S3 data processing assimilation scheme through process-based vegetation models that will deliver spatiotemporally highly resolved information on Europe’s vegetation productivity. To streamline all these datasets into a prototype vegetation productivity monitoring facility, new data processing concepts will be introduced such as the emulation of radiative transfer models.

Max ERC Funding

1 499 587 €

Duration

Start date: 2018-01-01, End date: 2022-12-31

Project acronymSUEE

ProjectStrategic Uncertainty in Economic Environments

Researcher (PI)Antonio Penta

Host Institution (HI)UNIVERSIDAD POMPEU FABRA

Call DetailsStarting Grant (StG), SH1, ERC-2017-STG

SummaryThis proposal concerns two sets of projects that tackle theoretical challenges raised by the data broker and online advertisement industry.
1-Strategic Uncertainty (SU) in Economic Environments: By assuming that individuals have correct beliefs about others' behavior, the equilibrium approach in economics assumes away SU. But SU is central to many settings. Testament to this is the existence of a data broker industry, in which data on agents' behavior are traded: this information would have no value without SU. Within game theory, non-equilibrium concepts such as rationalizability and models of level-k reasoning have been developed to study SU. But these models have had a limited impact on broader economics. This is partly due to the weakness and limited tractability of these concepts. Part 1 tackles SU in order to favor a better integration within economics. From a behavioral perspective, I propose axiomatic foundations that justify modeling individuals' reasoning as stemming from a cost-benefit analysis, and investigate (theoretically and experimentally) how these ideas shed light on the occurrence of equilibrium coordination under SU, i.e. as the result of purely subjective reasoning. From a classical perspective, I develop uniqueness and monotone comparative statics results for non-equilibrium concepts, to favor a better integration of SU in standard economics. Applications include problems of information disclosure of strategic datasets and identification in models of social interactions.
2-Online Auctions with Digital Marketing Agencies (DMA): I study the role of DMA in the auctions used to sell advertisement space on the web. I analyze how collusive bidding can emerge from bid delegation to a common DMA and how this undermines both revenues and efficiency of the auctions used by key players in the industry such as Facebook, Google and Microsoft-Yahoo!. Implications and extensions include business, policy and economics methodology.

This proposal concerns two sets of projects that tackle theoretical challenges raised by the data broker and online advertisement industry.
1-Strategic Uncertainty (SU) in Economic Environments: By assuming that individuals have correct beliefs about others' behavior, the equilibrium approach in economics assumes away SU. But SU is central to many settings. Testament to this is the existence of a data broker industry, in which data on agents' behavior are traded: this information would have no value without SU. Within game theory, non-equilibrium concepts such as rationalizability and models of level-k reasoning have been developed to study SU. But these models have had a limited impact on broader economics. This is partly due to the weakness and limited tractability of these concepts. Part 1 tackles SU in order to favor a better integration within economics. From a behavioral perspective, I propose axiomatic foundations that justify modeling individuals' reasoning as stemming from a cost-benefit analysis, and investigate (theoretically and experimentally) how these ideas shed light on the occurrence of equilibrium coordination under SU, i.e. as the result of purely subjective reasoning. From a classical perspective, I develop uniqueness and monotone comparative statics results for non-equilibrium concepts, to favor a better integration of SU in standard economics. Applications include problems of information disclosure of strategic datasets and identification in models of social interactions.
2-Online Auctions with Digital Marketing Agencies (DMA): I study the role of DMA in the auctions used to sell advertisement space on the web. I analyze how collusive bidding can emerge from bid delegation to a common DMA and how this undermines both revenues and efficiency of the auctions used by key players in the industry such as Facebook, Google and Microsoft-Yahoo!. Implications and extensions include business, policy and economics methodology.